Composition and method for reducing allergic response

ABSTRACT

A method and kit for the sequential early introduction to an infant of at least two allergens to decrease the infant&#39;s risk for developing allergies, the method involving administering an initial lower, exposure dose of a first allergen for a day or two, followed by administering a higher maintenance dose of the first allergen for several days, followed by administering the maintenance dose of the first allergen and an initial lower, exposure dose of a second allergen for a day or two, followed by administering the higher maintenance dose of the first allergen and a higher maintenance does of the second allergen for several days. The allergens can be provided in powdered protein form in premeasured pouches for addition to baby formula or to mother&#39;s milk. Alternatively, the allergens can already be provided in baby formula, or in other foods such as snack bars, cookies, or gels.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority from U.S. Provisional PatentApplication No. 62/595,290, entitled “COMPOSITION AND METHOD FORREDUCING ALLERGIC RESPONSE”, and filed Dec. 6, 2017.

FIELD OF THE INVENTION

The invention relates to allergies, and more particular an enteralcomposition and method for the sequential early introduction ofallergens to decrease a user's risk for developing food and otherallergies.

BACKGROUND OF THE INVENTION

Food allergies have become increasingly prevalent over the past twodecades, particularly in developed nations. One in thirteen children indeveloped nations have a food allergy, and all food allergies are causedby exposure to food proteins. Population studies from several countrieshave demonstrated this trend, including a rise in pediatrichospitalizations and anaphylaxis. Much work has been done to understandthe underlying mechanisms of food allergy and reasons for its increasingprevalence. Environmental factors and epigenetics have been implicatedas likely contributors. For instance, studies have shown that migrantsappear to acquire the incident risk of their adopted country, suggestinggenetics alone cannot explain the trend.

In recent times, infants are not being exposed to food the way they havebeen through most of human history. There is significant anthropologicevidence supporting the practice of early introduction of foods tobreastfed infants. Diet diversity has been a component of infant feedingfor most of human civilization for thousands of years, including throughmasticated foods given to infants for supplementation. It is likely thatthe movement away from these practices and other complementary feedingcustoms is correlated with increased food allergy incidence.

Recent randomized controlled trials on early introduction of highlyallergenic foods have shown a correlated reduction in food allergyincidence. In 2015, the Learning Early About Peanut Allergy (LEAP) trialdemonstrated a greater than 80% reduction in peanut allergy rates inthose infants exposed regularly to peanut protein compared to those whoavoided consumption. The following year, per-protocol results from TheEnquiring About Tolerance (EAT) study showed a two-thirds reduction offood allergy in those infants fed multiple food allergens regularlystarting at 3-4 months of age. These studies also inform an effectivequantity of allergen protein for administration to children in this agerange, in terms of grams per week sustained over time.

The scientific basis for these results can be found in the “dualallergen exposure hypothesis,” first described by Dr. Gideon Lack.According to this theory, exposure to allergens from cutaneous (skin)sources lends to sensitization and a higher risk of food allergydevelopment. On the other hand, exposure via the intestine (gut)promotes tolerance and is likely protective. By encouraging an extendedavoidance of allergenic foods, our previous medical dietary guidelinesmay have unwittingly promoted the increased rates of food allergybecause of decreased levels of gut tolerance in the population.

Based on the results of these significant trials, there has been aremarkable paradigm shift in how experts view the timing of foodallergen exposure to infants. This has resulted in the rapid evolutionof many US and international guidelines regarding infant dietrecommendations. In 2008, the American Academy of Pediatrics reversedits previous position where it had recommended avoidance of cow's milkfor 12 months, egg for 24 months, and nuts and fish for 36 months inhigh risk infants. In 2010, the National Institute of Allergy andInfectious Diseases (NIAID) issued new guidelines recommending againstthe delay of food introduction beyond four to six months of age. In2017, the NIAID further recommended early age-appropriate introductionof peanuts for all infants and especially in those at risk fordevelopment of food allergy. As recently as Sep. 7, 2017, the FDA issuedits first-ever qualified health claim advising that early introductionof peanuts to certain high-risk infants may reduce the risk of peanutallergy. Other countries have issued similar guidance, including anAustralian Consensus stating that “all infants should be givenallergenic solid foods including peanut butter, cooked egg, dairy, andwheat products in the first year of life. This includes infants at highrisk of allergy.” Thus, the extent to which guidance from pediatriciansand allergists regarding early introduction has shifted cannot beoverstated and we are looking at a sea change in approach from just adecade ago.

Unfortunately, early introduction is difficult to accomplish, and thereis still no mechanism for families to achieve easy and effective earlyintroduction of multiple food allergens for their babies. While initialstudy protocols (such as LEAP and EAT) have been effective, they arevery difficult to comply with. In the case of LEAP, parents werecontacted 104 times over the course of the study to ensure compliance.For the EAT study, only 56% of parents were able to maintain the feedingrequirements, which included fairly large amounts of solid foods ininfants who had not started eating otherwise and had certaindifficulties doing so. For the EAT study, this was a critical factor:the reduction in food allergy was only shown to be statisticallysignificant in the group of families who were able to maintain a certainlevel of compliance. Any family can attest to the difficulty of gettingyoung children to consistently eat one food, let alone multiple,especially at such a young age.

Furthermore, there are many children who have already developed signs offood allergy on testing by the age of six months. This is telling usthat even with these newer efforts, we are not starting early enough. Inthe LEAP study, 9% of children with allergy risk factors were excludedat enrollment because they already tested positive for peanut allergy onskin prick testing. As described further below, the inventors havediscovered that very early introduction of allergenic proteins, perhapsto newborn or infants within the first weeks of life, may be anappropriate time to start the introduction.

A population level intervention is needed for significant improvement inthe food allergy epidemic. Traditionally defined “high risk” childrenonly represent a minority of the total food allergy population. Evenwith rigorous early introduction studies, some enrolled infants alreadydemonstrated positive food challenges, suggesting earlier ages ofexposure would be merited. Moreover, currently utilized food allergytesting has significant limitations. It is not necessary and certainlynot feasible for every infant to see an allergist before starting toeat. In fact, there are significant downsides of excessive screeningtests for food allergy, such as skin prick tests, which can triggerrecommendations to avoid certain foods which otherwise would not produceclinical symptoms of food allergy.

These issues are compounded because it appears that there is arelatively narrow immunological developmental window during whichinfants can acquire their ability to handle allergens without havingallergic reactions. If this immunological developmental window ismissed, e.g., because of avoidance of allergens, it may be too late.

While it would be desirable to ameliorate this problem by introducingsolid foods at an early age, this can be a challenge because manyinfants are not yet developmentally ready for solid food, and it can bedifficult for busy parents with young infants to stick to a regimen.

Accordingly, there remains a need for compositions and methodology forintroducing multiple food allergens (at specified dose amounts ofprotein) to infants younger than 6 months of age that also simplifiesand helps standardize early exposure and limit the need for universalscreening or other unrealistic and unreliable public health measures.

SUMMARY OF THE INVENTION

The present invention is a multiple allergen early introduction system,in the form of a kit which includes an outer container (box, bag, pouch,tin) containing individually packaged single use portions,preferentially in a stick pack with protein powders and othersubstances. The protein powders are formulated to readily suspend inbreastmilk or infant formula and are of a particle size that readilypasses through the nipple of common infant bottles. These componentsachieve their purpose through adherence to the daily and guided systemof early introduction. During the exposure phase, food proteinsrepresenting major food allergens are introduced one by one and withgraded dose increases with a stepwise daily packet. Additional foodallergens are added over the course of multiple days. During themaintenance phase, sustained amounts of all of the relevant foodallergens are administered through ongoing daily packets. These arecontinued daily until routine diet diversity is achieved from theregular consumption of solid foods.

In lieu of providing the multiple allergen early introduction system inthe form of a kit which includes an outer container (box, bag, pouch,tin) with individually packaged single use portions, which are to beadded by the users to infant formula or mother's milk, the multipleallergens can be provided as already mixed in with infant formula. Forexample, infant formula could be provided in a staged kit, with theinfant formula progressing through different formulations that introduceand then bring up the level of the various allergens until a final,maintenance infant formula is reached, and then that maintenance infantformula can continue to be given to the infant for a time. In additionto a staged kit, an infant formula containing a maintenance level of themultiple allergens at their maintenance doses can be provided. Theadvantage of such a maintenance level of such a formulation would bethat once the maintenance level of the allergens is reached, this wouldobviate the need for consumers to add the single use portions ofmultiple allergens each time a bottle of infant formula is prepared.

Another embodiment of the invention can include providing a kit of theallergens as noted above, but instead of providing the allergens inpre-measured dry powders to be added to infant formula or mother's milk,they can be provided as individually packaged single use gels portionswhich can be administered into the infant's mouth during feedings.

A further embodiment of the invention can include providing the multipleallergens in pre-prepared foods, such as providing the multipleallergens in baby food in jars, pouches, packs, etc., or in the form ofsnack bars, “cookies”, and the like. Such forms would be especiallyappropriate for infants once they begin eating baby food and would beideal for formulations at the maintenance level of allergens.

The system may also have one or more of the following: (a) Exposurepackets and maintenance packets that can be introduced earlier thancurrent national feeding guidelines of four (4) months, should theseguidelines change. Indeed, the inventors have determined that someinfants are already sensitized to certain allergens, e.g., peanuts, atthe age of four months and therefore believe that the allergens of theinvention should start to be administered to infants earlier than fourmonths, and perhaps as early as the first days or weeks of life. Indeed,the same formulation could be used as early as the neonatal period. (b)Exposure and maintenance packets that can also be mixed in solid foods,if the infant is developmentally ready. (c) Exposure and maintenancepowders pre-mixed in liquid, such as water or liquid infant formula. (d)Exposure and maintenance powders in a slurry formulation, for additionalroutes of administration, including via a daily dispensing pacifier. (e)Other non-protein additives to boost immune and intestinal health duringearly introduction. These may include but are not limited to: one ormore vitamins, such as Vitamin D3, live cultures, probiotics, orprebiotics. (f) Other non-protein additives for use as a dietarysupplement, including but not limited to: stabilizers, emulsifiers,anti-caking agents, sweeteners, or flavoring. (g) A supplement kit ofadditional food allergens for use after certain time has elapsed on themaintenance phase. These food allergens can include but are not limitedto: tree nuts, whitefish, shellfish, wheat, soy, and sesame. Thissupplement kit would likewise be in the form of a kit which includes anouter container (box, bag, pouch, tin) containing individually packagedsingle use portions, preferentially in a stick pack with protein powdersand other substances. (h) A supplement kit of additional non-foodallergens deemed appropriate for early introduction, including but notlimited to: pet and other non-food animal allergens, pollen and otherseasonal allergens, or medication allergens.

These and other features of the invention are described below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a table showing the dosing regimen for an exemplarythree-allergen early introduction kit of the invention.

FIG. 2 is a table showing the dosing regimen for an exemplaryfive-allergen early introduction kit of the invention.

FIG. 3 is front of three stick packs marked with day number for anexemplary formulation of the kit of invention.

DETAILED DESCRIPTION

The invention is a ground-breaking solution to the difficulties infantcaretakers face with early food introduction for infants. It is adietary supplement aimed at broad adoption and a substantial reductionof food allergies on a population level. This supplement, a powder thatmixes easily with breast milk or formula or in infant foods, includes“culprit allergens” from the foods most commonly associated withchildhood food allergy. Made from the powder of natural foods, the dailydose regimen has been formulated specifically to promote the developmentof tolerance via the gastrointestinal system. While it is impossible toprevent all reactions to food, our dosing regimen is specificallydesigned to ensure that reactions are mild and identified early, if theyoccur. In addition to the evidence-based dose escalation noted above,another innovative feature involves sequential introduction of foodallergens.

Through easy-to-follow daily use with breastmilk or formula, starting atabout four months of age, infants will be exposed to common foodallergens during the key critical window of immune development. In oneembodiment of the invention, the maintenance formulation includes threeallergens, namely cow's milk, egg, and peanut, which together representover 80% of all childhood food allergies. It is noted that while cow'smilk is used, cow's milk yogurt or whey and casein powder can be usedinstead. Other kits can encompass additional proteins, addressing thevast majority of all causes of IgE-mediated food allergy. The dosingregimen is evidence-based, drawn from the methodology of recentrandomized trials as well as published clinical experience with oralfood challenges in allergists' offices. Parents and other caregivers cantake comfort in a dosing regimen developed by allergists, specificallydesigned to reduce the risk of food allergy development and with safetyas the constant priority.

What the invention is not, is the introduction of microdoses orhomeopathic approaches. There is a widely-described concern amongallergists that introducing allergens at doses that are 1) too low and2) too infrequent can in fact promote the sensitization pathway andtherefore increase rather than reduce food allergy incidence. Throughthe innovative, gentle and gradual daily dosing regimen, the inventorshave maximized the efficacy of the method and kit while adhering tostrict safety considerations.

In a preferred embodiment, the multiple allergen early introductionsystem is a kit comprising daily dietary supplements and instructionsfor use. The system is a stepwise program of daily use, administered toinfants via suspension of the supplement powder in breast milk, formula,or solid foods. The daily program incorporates increases in proteinexposure, sequential introduction, and promotion of tolerance. Firstexposure formulations use protein amounts determined to be in a range oflow provoking doses, as established in the medical literature. Byutilizing low provoking doses, reactions if they do occur aresignificantly more likely to be mild in nature. In the event of anyreaction, including but not limited to rashes or gastrointestinal upset,parents and other caregivers are able to present an exact description ofexposure history to their pediatrician or allergist. This approach istruly ground-breaking in its ability to reduce the burden of confusingand inconsistent testing that children face when they experience anyfood reactions in current practice. Focused testing is proven to be thebest approach to allergy diagnosis, and our dosing regimen allowsfamilies to do just that.

After it has been confirmed that the exposure dose of a particularprotein is well tolerated, the infant will continue to be given packetsof protein, which subsequent packets will include a higher,“maintenance” dose of the now cleared protein. Thus, each day'ssupplement involves either 1) duplication of previous allergen amountsto promote tolerance and allow for detection of delayed reactions, 2)increase of previous allergen amount to achieve maintenance dosinglevels, or 3) addition of a new food allergen for sequentialintroduction. Once an allergen has been introduced, it is included inall subsequent days of the guided program.

The “exposure” phase involves graded increases in allergen amount aswell as sequential introduction of new allergens. Once maintenancelevels of each have been attained, continuation at these levels is donethrough daily administration during the “maintenance” phase. Anexemplary introduction kit contains a 30-day supply consisting of dailysupplements for both the exposure and maintenance phase. Busy mothers,whether breastfeeding, pumping, formula feeding, or some combination ofthese three, will benefit from the ease of use of the kit and method.Moreover, absolutely no changes in feeding practices are needed for thisprogram. The product's powder comes in easily portable packets and noextra supplies are needed.

Continuation kits contain the maintenance phase formulations only. Theformulations and duration of the exposure phase depends on the numberand type of allergens introduced. FIG. 1 is an exemplary dosing chartfor a three-allergen introduction system. FIG. 1 is illustrative, butthe guided system is not limited to a three-allergen system and themethod described above applies to additional allergens as well.

The dosing chart includes initial dosing derived from “low provokingdose” data as well as protocols from food allergy prevention studiesincluding LEAP, EAT, and PETIT.

The food allergen proteins are sourced from the powders of whole foods.These whole food powders are verified to be pure and limited to thespecific whole food as well as produced via good manufacturingpractices. For the referenced exemplary three-allergen example, theprotein powders consist of organic cow's milk, organic cooked egg white,and organic peanut powder.

FIG. 1 lists the representative protein components of a three-allergenearly introduction system. The daily supplement can also include 400 IUof Vitamin D3, probiotics including but not limited to Streptococcusthermophilus and Lactobacillus delbrueckii ssp bulgaricus (both of whichare used in the production of cow's milk yogurt) and Bifidobacteriuminfantis. The powders are preferably made by known techniques includingfreeze or spray drying, milling, sifting, vibratory sifting, and vacuumodor removal of the various products

In its most complete form, the kit of the invention is made up of thefollowing components. Daily supplements are provided in the form of apowder contained within a specifically labeled package, such as a stickpack or sealed pouch. Hereinafter the inventor refers to the packagingas a stick pack but the format can be as desired. The stick packspecifies the day within the guided system, preferably both throughverbiage and pictorially, e.g., DAY 1, DAY 2, . . . DAY 30. The stickpacks themselves may preferably be arranged within a box with adesignated sequence. The box contains written instructions printed onthe packaging as well as an insert. Combined, these components make upthe multiple allergen early introduction system kit.

The most complete form of performing the method associated with thedisclosed device consists of the following steps: On a daily basis, andaccording to the instructions for use, the infant's creative is to tearopen the indicated stick pack, empty its contents into either 1) aninfant bottle containing breast-milk, 2) an infant bottle containinginfant formula, or 3) a bowl of infant food. For options 1) and 2), thebottle is to be swirled gently until the powder is in suspension. Foroption 3), the content is stirred into the infant food. The bottle orinfant food is then to be preferably given to the infant within fiveminutes. If there is a delay in administration or any settling isnoticed, the bottle will again be swirled gently prior to feeding. Theentire contents of each stick pack are to be consumed by the infantdaily during the guided system. Empty stick packs are to be disposed.

The maintenance phase stick packs are to be continued daily until theinfant is tolerating a wide range of solid foods ensuring dietdiversity. Once the initial introduction kit has been completed,subsequent multiple allergen supplements will be available through30-day maintenance kits.

Turning back to FIG. 1, it is a table that illustrates an exemplarydosing regimen for a three-allergen early introduction system, which isone particular version of the kit. According to this embodiment, theamount and type of protein is listed alongside the day of the guidedprogram. Day 1 is the exposure dose of cow's milk protein. Day 2 repeatsthis dose for promotion of tolerance as well as for identification ofdelayed reactions. The inventor considers two days at the exposure doseto be long enough for the infant's caregiver to observe if there hasbeen any delayed reaction, yet not unnecessarily prolonging the time toreach the maintenance dose. Day 3 increases this dose as part of thegraded introduction method. Day 4 repeats Day 3's dose for promotion oftolerance as well as for identification of delayed reactions. Theexposure dose of the cow's milk powder protein will preferably be givenfor two days and will range between about 0.05 and 0.5 grams and willpreferably be about 0.2 grams, with the exposure dose being increasedafter two days to the maintenance dose, which will range between about0.2 and 1 grams and will preferably be about 0.57 grams. Day 5 includesthe previous maintenance dose of cow's milk protein, with the additionof an exposure dose of cooked egg white protein. Day 6 includes theprevious maintenance dose of cow's milk protein, and repeats Day 5'sdose of cooked egg white protein for promotion of tolerance as well asfor identification of delayed reactions. Days 7 and 8 include theprevious maintenance dose of cow's milk protein with the addition of amaintenance dose of cooked egg white protein. The exposure dose of thecooked egg white powder protein will preferably be given for two daysand will range between about 0.01 and 0.1 grams and will preferably beabout 0.025 grams, with the exposure dose being increased after two daysto the maintenance dose, which will range between about 0.05 and 0.5grams and will preferably be about 0.125 grams. Days 9 and 10 includethe previous maintenance doses of cow's milk protein and cooked eggwhite protein, with the addition of an exposure dose of peanut proteinwhich will range between about 0.05 and 0.3 grams and will preferably beabout 0.1 grams. For days 11 and 12, the packets will include theprevious maintenance doses of cow's milk protein and cooked egg whiteprotein, with the addition of a maintenance dose of peanut protein whichwill range between about 0.1 and 0.9 grams and will preferably be about0.43 grams. Days 13-30 will follow the same pattern of graded andsequential introduction, until maintenance dosing of milk, egg, andpeanut is achieved, and represents the maintenance phase of the system.

Although the chart in FIG. 1 shows first the introduction of cow's milkprotein, then cooked egg white protein, and lastly peanut protein, therelative order of the introduction of the cow's milk protein, cooked eggwhite protein, and peanut protein may not be important and can thus beswapped around; such as first cooked egg white protein, second peanutprotein cow's, and third cow's milk protein, or first cooked egg whiteprotein, second peanut protein cow's, and third milk protein, or firstpeanut protein, second cow's milk protein, and last cooked egg whiteprotein, etc.

The staged dosing for the various packages described with reference toFIG. 1 are for cow's milk powder, chicken egg powder, and peanut powder.In another embodiment of the invention, the kit and method comprisesthese three basic protein powders plus one or more additional powderscontaining different food allergens which can be introduced either afterthe initial cow's milk powder, chicken egg powder, and peanut powder, oreven before and/or interspersed with dosing with the cow's milk powder,the chicken egg powder, and the peanut powder. However, since cow'smilk, chicken egg, and peanut allergies as a group constitute about 80%of the common food allergies of childhood, it makes sense to introducethese allergens first. Alternately, in a further embodiment of theinvention, the kit and method comprises the administration of theadditional powders which will be introduced after the infant has firstconsumed the starter kit with cow's milk powder, the chicken egg powder,and the peanut powder.

Turning now to the additional powders, they can include tree nutspowder. Some common tree nuts that cause allergies include almonds,Brazil nuts, cashews, chestnuts, filberts/hazelnuts, macadamia nuts,pecans, pistachios, pine nuts, shea nuts and walnuts. Since some peopleare allergic to some but not all tree nuts, in practice the additionalpowder will include a blend of different powdered tree nuts. Theseadditional powders can also include whitefish powder. Whitefish is afisheries term for several species of demersal fish with fins,particularly Atlantic cod (Gadus morhua), Caspian kutum (Rutilus kutum),whiting (Merluccius bilinearis), and haddock (Melanogrammus aeglefinus),but also hake (Urophycis), pollock (Pollachius), or others. Thewhitefish powder is made from at least one of these dehydrated fishspecies. These additional powders can likewise include shellfish powder.Shellfish includes shelled mollusks such as abalone, clams, mussels,oysters, scallops and cockles, and crustaceans, such as crabs, shrimps,prawns, lobsters, and crawfish. Most allergies from shellfish are tocrustaceans. The shellfish powder can constitute shellfish which isdehydrated and ground to a fine powder. Lastly, the additional powdercan comprise wheat powder, soy protein powder, and/or sesame powder. Thedoses selected for these additional protein powders will be determinedbased on data regarding provoking doses of each protein and the highermaintenance dose for each protein. These additional proteins will beintroduced in the same staged manner with a first lower provoking dosefor one and preferably two to three days, followed by the highermaintenance dose that will continue.

FIG. 2 is a chart showing a dosing schedule for an exemplary embodimentof a five allergen early introduction system kit, with the allergensbeing in cow's milk powder, chicken egg white powder, peanut powder,wheat powder, and soy powder. As noted above, the relative order ofadministration of the cow's milk powder, chicken egg white powder,peanut powder, wheat powder, and soy powder can be shifted. In thisexemplary embodiment, the dosing of the cow's milk powder, chicken eggpowder, peanut powder can remain the same as in the three allergen earlyintroduction system kit as in FIG. 1. The dosing of the wheat powder andsoy powder will be as follows. The exposure dose of the wheat powderprotein will preferably be given for two days (beginning on day 13) andwill range between about 0.05 and 0.5 grams and will preferably be about0.1 grams, with the exposure dose being increased after two days to themaintenance dose (beginning on day 15), which will range between about0.2 and 1 grams and will preferably be about 0.4 grams. Packets of theproduct will continue to include the maintenance dose of the wheatpowder. Next, the exposure dose of the soy powder protein willpreferably be given for two days (beginning on day 17) and will rangebetween about 0.05 and 0.5 grams and will preferably be about 0.1 grams,with the exposure dose being increased after two days (beginning on day19) to the maintenance dose, which will range between about 0.2 and 1grams and will preferably be about 0.4 grams. Once the maintenance doseis reached (day 19), all subsequent packets of the product will continueto include the maintenance doses of all the allergen containing powders.

FIG. 2 describes a kit with powders containing five allergens, viz.,cow's milk, chicken egg white, peanut, wheat, and soy. Other kits arecontemplated consisting of other noted food allergens. However,regardless of the kit, each allergen will be introduced in a firstintroductory, lower dose, which after at least one day, and preferablytwo days, will be increased to a higher maintenance dose. It is alsopossible that an intermediate dose be given, or that the maintenancedose can be increased gradually in additional steps.

Turning to FIG. 3, there is shown three stick packs for Day 1, Day 2,and Day 3 of an exemplary kit of the invention, which would preferablycontain 30 such packs, each sequentially numbered, and containing theamount of allergen containing powder as noted in FIG. 1. Accordingly,the various stick packs will contain the various powders containing theallergen(s) in pre-dosed sticks packs, each bearing its unique number sothat the infant's caregiver will know which package to mix in withbreastmilk, formula, or baby food on which day.

In another preferred embodiment of the invention, the multiple allergenearly introduction system comprising daily dietary supplements for usein a stepwise program of daily use, administered to infants. However,unlike the earlier described embodiment, the dietary supplements arepre-incorporated in the appropriate doses in infant formula, in solidfoods (e.g., baby food in jars, pouches, cookies and snack bars and thelike, and other food items), or in pre-dosed gel packs so that thecaregiver does not need to mix separate supplements into the food. As inthe earlier described embodiment, the daily program incorporatesincreases in protein exposure, sequential introduction, and promotion oftolerance. First exposure formulations use protein amounts determined tobe in a range of low provoking doses, as established in the medicalliterature. By utilizing low provoking doses, reactions if they do occurare significantly more likely to be mild in nature. In the event of anyreaction, including but not limited to rashes or gastrointestinal upset,parents and other caregivers are able to present an exact description ofexposure history to their pediatrician or allergist. After it has beenconfirmed that the exposure dose of a particular protein is welltolerated, the infant will continue to be administered the infantformula, solid foods, or the pre-dosed gel packs packets containing theprotein(s), which subsequent infant formula, solid foods, or thepre-dosed gel packs packets containing the protein(s) will include ahigher, “maintenance” dose of the now cleared protein. Thus, each day'sfood with the supplement involves either 1) duplication of previousallergen amounts to promote tolerance and allow for detection of delayedreactions, 2) increase of previous allergen amount to achievemaintenance dosing levels, or 3) addition of a new food allergen forsequential introduction. Once the food with an allergen has beenintroduced, it is included in all subsequent days of the guided program.

The “exposure” phase involves graded increases in allergen amount aswell as sequential introduction of new allergens. Once maintenancelevels of each have been attained, continuation at these levels is donethrough daily administration during the “maintenance” phase of the food.

An exemplary introduction kit contains a 30-day supply consisting ofdaily food items containing the supplements for both the exposure andmaintenance phase. Continuation kits contain the maintenance phase foodwith formulations only can also be provided.

The formulations and duration of the exposure phase depends on thenumber and type of allergens introduced. The dosing of the variousallergens can follow the same exemplary dosing chart as provided in FIG.1 for a three-allergen introduction system. Again, FIG. 1 isillustrative, and the guided system is not limited to a three-allergensystem and the method described above applies to additional allergens aswell.

As discussed, the invention has many different features, variations andmultiple different embodiments. The invention has been described in thisapplication at times in terms of specific embodiments for illustrativepurposes and without the intent to limit or suggest that the inventionconceived is only one particular embodiment. It is to be understood thatthe invention is not limited to any single specific embodiments orenumerated variations. Many modifications, variations and otherembodiments of the invention will come to mind of those skilled in theart to which this invention pertains, and which are intended to be andare covered by both this disclosure. It is indeed intended that thescope of the invention should be determined by proper interpretation andconstruction of the disclosure, including equivalents, as understood bythose of skill in the art relying upon the complete disclosure at thetime of filing.

The disclosed method and kit is unique when compared with other knownmethods and kits solutions because it provides an opportunity for earlyintroduction of multiple allergens to infants even prior to when theymay be developmentally ready for solid food, via easy suspension inbreast milk or infant formula, or provided already mixed in with food.The use of multiple allergens addresses the majority of food allergycauses rather than just one allergen. As noted above, the preferredembodiment with the three common allergens in cow's milk, hen's eggwhites, and peanuts, this represents the foods responsible for >80% ofchildhood food allergy. Similarly, the method is unique in thatintroduction is in a graded dose increase fashion, facilitating promptand early identification of potential allergic reactions which if theyoccur, are more likely to be mild. Similarly, the disclosed method isunique when compared with other known processes and solutions in thatmultiple allergens are introduced in a sequential fashion, so thespecific food allergen involved in potential reactions can beidentified.

The disclosed kit is unique in that it is structurally different fromother known devices or solutions. More specifically, the kit is uniquedue to the presence of multiple allergens within the maintenance phaseof the guided system kit. The daily formulations consist of unique anddistinct doses to achieve sequential as well as graded introduction,based on protocols from the early introduction literature. Thecomponents of the daily powders are of sufficiently low particle size,in particular less than about 200 microns, to allow for easy passagethrough infant bottle nipples. Furthermore, the formulations arespecifically designed and tested to allow for easy mixing with breastmilk or infant formula. Regarding the kit, a variety of verbal andpictorial instructions allow for easy compliance with the sequence ofdaily administration.

Furthermore, the process and method of using the kit is likewise unique.More specifically, the disclosed process and method owes its uniquenessto the fact that it provides families with detailed information on theprecise identity and amount of food allergen exposure, in the event ofadverse food reactions, to be provided to relevant healthcareprofessionals. Based on the day of the program, families know exactlywhich food allergens have been administered, how much, and when. Anyother approach that does not stagger the introduction of individualallergens over a time series would not offer this benefit of tracingadverse reactions to their cause.

The preferred embodiments of this invention have been disclosed,however, so that one of ordinary skill in the art would recognize thatcertain modifications would come within the scope of this invention.

What is claimed is:
 1. A kit for the introduction of premeasured dosesof at least two different allergens to an infant to decrease theinfant's risk for developing allergies, the kit comprising: one or morefirst pre-dosed packages comprising a first allergen at an exposuredose; one or more second pre-dosed packages comprising the firstallergen at a maintenance dose; one or more third pre-dosed packagescomprising the first allergen at a maintenance dose and a secondallergen at an exposure dose; and one or more fourth pre-dosed packagescomprising the first allergen at a maintenance dose and the secondallergen at a maintenance dose; wherein the first, second, third andfourth pre-dosed packages are identified so that user will know theorder of administration of the various packets; wherein the exposuredoses of one or more of the allergens may optionally be graduallyincreased; and wherein the exposure dose of the first allergen and theexposure dose of the second allergen are lower than the maintenance doseof the first allergen and the maintenance dose of the second allergen,respectively.
 2. The kit of claim 1, wherein the first and secondallergens are each selected from the group consisting of cow's milk,egg, peanut, wheat, soy, sesame, fish, shellfish, and tree nuts.
 3. Akit for the introduction of premeasured doses of at least threedifferent allergens to an infant to decrease the infant's risk fordeveloping allergies, the kit comprising: one or more first pre-dosedpackages comprising a first allergen at an exposure dose; one or moresecond pre-dosed packages comprising the first allergen at a maintenancedose; one or more third pre-dosed packages comprising the first allergenat a maintenance dose and a second allergen at an exposure dose; and oneor more fourth pre-dosed packages comprising the first allergen at amaintenance dose and the second allergen at a maintenance dose; one ormore fifth pre-dosed packages comprising the first allergen at amaintenance dose, the second allergen at a maintenance dose, the thirdallergen at an exposure dose; and one or more sixth pre-dosed packagescomprising the first allergen at a maintenance dose, the second allergenat a maintenance dose, and the third allergen at a maintenance dose;wherein the first, second, third, fourth, fifth, and sixth pre-dosedpackets are identified so that user will know the order ofadministration of the various packets; wherein the exposure doses of oneor more of the allergens may optionally be gradually increased; andwherein the exposure dose of the first allergen, the exposure dose ofthe second allergen, and the exposure dose of the third allergen arelower than the maintenance dose of the first allergen, the maintenancedose of the second allergen, and the maintenance dose of the thirdallergen, respectively.
 4. The kit of claim 3 wherein the first allergencomprises cow's milk and the exposure dose of the first allergen isbetween 0.05 and 0.5 grams of cow's milk protein, wherein themaintenance dose of the first allergen is between 0.2 and 1 grams ofcow's milk protein, wherein the second allergen comprises egg and theexposure dose of the second allergen is between 0.01 and 0.1 grams ofegg protein, wherein the maintenance dose of the second allergen isabout between 0.05 and 0.5 grams of egg protein, wherein the thirdallergen comprises peanut and the exposure dose of the third allergen isbetween 0.05 and 0.3 grams of peanut protein, and wherein themaintenance dose of the third allergen is between 0.1 and 0.9 grams ofpeanut protein.
 5. A kit for the introduction to an infant of at leasttwo allergens to decrease the infant's risk for developing allergies,the kit comprising: one or more first type of food packages comprising aquantity of food and a first allergen at an exposure dose; one or moresecond type of food packages comprising a quantity of food and the firstallergen at a maintenance dose; one or more third type of food packagescomprising a quantity of food, the first allergen at a maintenance dose,and a second allergen at an exposure dose; and one or more fourth typeof food package comprising a quantity of food, the first allergen at amaintenance dose, and the second allergen at a maintenance dose; whereinthe first, second, third and fourth type of food packages are identifiedso that user will know the order of administration of the various foodpackages; wherein the exposure dose of the first allergen and theexposure dose of the second allergen are lower than the maintenance doseof the first allergen and the maintenance dose of the second allergen,respectively.
 6. The kit of claim 5, further comprising a fifth type offood package comprising a quantity of food along with the first allergenat a maintenance dose, the second allergen at a maintenance dose, and athird allergen at an exposure dose; and one or more sixth type of foodpackages comprising a quantity of food along with the first allergen atthe maintenance dose, the second allergen at a maintenance dose, and thethird allergen at a maintenance dose; wherein the fifth and sixth typeof food packages are identified so that user will know the order ofadministration of the various food packages; wherein the exposure dosesof one or more of the allergens may optionally be gradually increased;and wherein the exposure dose of the third allergen is lower than themaintenance dose of the third allergen.
 7. The kit of claim 6 whereinthe first allergen comprises cow's milk and the exposure dose of thefirst allergen is between 0.05 and 0.5 grams of cow's milk protein,wherein the maintenance dose of the first allergen is between 0.2 and 1grams of cow's milk protein, wherein the second allergen comprises eggand the exposure dose of the second allergen is between 0.01 and 0.1grams of egg protein, wherein the maintenance dose of second allergen isbetween 0.05 and 0.5 grams of egg protein, wherein the third allergencomprises peanut and the exposure dose of the third allergen is between0.05 and 0.3 of peanut protein, and wherein the maintenance dose ofthird allergen is between 0.1 and 0.9 grams of peanut protein.
 8. Thekit of claim 5, wherein the food packages comprise infant formula,infant food in jars, pouches, snack bars, cookies, or a gel.
 9. The kitof claim 5, further comprising: (a) one or more additional food packagescomprising quantities of food, an additional allergen at an exposuredose, and maintenance doses of the allergens in the previous foodpackages; and (b) one or more additional food packages comprisingquantities of food, the additional allergen at a maintenance dose, andmaintenance doses of the allergens in the previous food packages; andwherein the exposure dose of the additional allergen is lower than themaintenance dose of the additional allergen.
 10. The kit of claim 9,comprising further additional food packages with allergens at an initiallower exposure dose and additional food packages with allergens at ahigher maintenance dose.
 11. The kit of claim 3 wherein the saidallergens are each selected from the group consisting of cow's milk,egg, peanut, wheat, soy, sesame, fish, shellfish, and tree nuts.
 12. Thekit of claim 1, wherein the allergens consist of particles having aparticle size of less than 200 microns.
 13. The kit of claim 3, whereinthe allergens consist of particles having a particle size of less than200 microns.
 14. The kit of claim 3, wherein the exposure dose of eachallergen is between 0.01 and 0.3 grams and the maintenance dose of eachallergen is between 0.05 and 1 grams.
 15. The kit of claim 1, whereinthe premeasured doses are in a form of a) pre-dosed daily packets,packages, or pouches, b) measured powder supplements, c) gels, d) infantformula or e) other foods.
 16. The kit of claim 3, wherein thepremeasured doses are in a form of a) pre-dosed daily packets, packages,or pouches, b) measured powder supplements, c) gels, d) infant formulaor e) other foods.
 17. The kit of claim 3, wherein the premeasured dosesare in the form of sequentially numbered packages so that users areguided when to administer each respective package.